The projects outlined in this application are the outgrowth of a synthesis of 5'(R)-(2H1)-adenosine devised by the principal investigator in 1978. Since that time, the chirally labeled adenosine has been utilized to elucidate the stereochemistry of three important enzyme-catalyzed reactions, including the one catalyzed by S-adenosylhomocysteine hydrolase. Future studies of S-adenosylhomocysteine hydrolase will examine the mechanism of action of a new irreversible inhibitor of this enzyme recently prepared in our laboratories. In addition, the biosynthesis of two unusual nucleosides will be investigated. The first of these is the antiviral nucleoside sinefungin. Preliminary evidence obtained in our laboratory supports a hypothesis proposed by investigators at Eli Lilly, namely, that this nucleoside is formed by a novel C-C bond formation between C-5 of ornithine and C-5' of adenosine. The second nucleoside proposed for investigation is the insecticidal compound thuringiensin. The most mechanistically interesting feature of this nucleoside is the presence of an ether linkage between C-5' of adenosine and C-4 of glucose. The biosynthesis of both sinefungin and thuringiensin will be investigated by administration of precursors specifically labeled with either radioactive or stable isotopes to the producing organisms. Precursors that are doubly-labeled either with two radioisotopes or with two stable isotopes will also be used.